John O’Keefe

John O’Keefe (born November 18, 1939, New York City, New York, U.S.) is a British-American neuroscientist who contributed to the discovery of place cells in the hippocampus of the brain and elucidated their role in cognitive (spatial) mapping. O’Keefe’s investigations of impairments in the cognitive mapping abilities of rats had important implications for the understanding of Alzheimer disease and other human neurological conditions in which affected persons fail to recognize their surroundings. For his contributions to the understanding of neural processes involved in the mental representation of spatial environments, O’Keefe shared the 2014 Nobel Prize for Physiology or Medicine with Norwegian neuroscientists May-Britt Moser and Edvard I. Moser.

O’Keefe grew up in New York City, the son of Irish immigrants. He studied aeronautical engineering at New York University before enrolling in 1960 at the City College of New York (CCNY) to study philosophy of the mind. After earning a bachelor’s degree from CCNY in 1963, he went to McGill University in Montreal, where he carried out graduate studies in the school’s psychology department. At McGill O’Keefe worked in the laboratory of Canadian psychologist Ronald Melzack, researching the sensory properties of the amygdala (a part of the brain involved in the fight-or-flight response) and developing tools and methods for his investigations. He completed a doctorate degree in physiological psychology in 1967, that same year joining University College London (UCL) as a postdoctoral research fellow. He remained at UCL for the duration of his career, eventually serving as a professor of cognitive neuroscience.

Within a few years at UCL, O’Keefe shifted his research from the amygdala to the hippocampus, attempting to understand its role in animal behaviour. Using techniques to record the activity of individual neurons in the rat hippocampus, he was able to observe the responses of single cells and correlate their activity to specific behaviours. Of particular interest to O’Keefe were rats that had sustained damage to the hippocampus, which produced significant changes in behaviour, such as reduced performance on spatial tasks and hyperactivity in new environments. After many experiments, O’Keefe discovered that cell activity in certain areas of the hippocampus was a function of place, with activity related specifically to where an animal was in its environment. The particular hippocampal areas involved (e.g., CA1) were densely occupied by pyramidal cells—cells that in the context of orientation and navigation became known as place cells. In 1971, with his student Jonathan O. Dostrovsky, O’Keefe published his findings, proposing in their seminal paper that behavioral deficits in animals with hippocampal damage stemmed from the loss of neural systems involved in cognitive mapping.

In 1978 O’Keefe and colleague Lynn Nadel published The Hippocampus as a Cognitive Map, describing in detail a theory that placed the cognitive map—the existence of which was first proposed in 1948 by American psychologist Edward C. Tolman—specifically in the hippocampus. The theory met with skepticism but later gained support through key discoveries by other researchers, including the Mosers’ discovery in 2005 of grid cells—cells located in a part of the brain known as the dorsocaudal medial entorhinal cortex (dMEC) that produce a system of coordinates by which animals determine their spatial position and navigate their environment. Subsequent research revealed that place cells and grid cells interact, with the activity of place cells likely derived from the formation of grids.

The neural system elucidated by O’Keefe and colleagues was described popularly as an “inner GPS.” O’Keefe’s research was crucial in that it provided the first experimental evidence for such a system and offered insight into the ability of animals, including humans, to orient themselves within an environment, to navigate from one place to another, and to remember spatial information. The loss of those abilities in humans is a hallmark of neurological disease, particularly Alzheimer disease, for which O’Keefe’s findings opened up new avenues of research. His work also fueled progress in scientists’ understanding of human cognition, especially aspects of memory.

In addition to the Nobel Prize, O’Keefe was the recipient of other prestigious awards, including the 2013 Louisa Gross Horwitz Prize (shared with the Mosers) and the 2014 Kavli Prize in Neuroscience (shared with Canadian neuropsychologist Brenda Milner and American neurologist Marcus Raichle). O’Keefe was elected a fellow of the Royal Society in 1992 and of the U.K. Academy of Medical Sciences in 1998.